Genetics

Certain individuals are genetically susceptible to developing autoimmune diseases. This susceptibility is associated with multiple genes and other risk factors. In many autoimmune diseases three main sets of genes are suspected. These genes are related to:1

Although a predisposition to autoimmune disease can run in families, some family members can be affected by different disorders; for example, one person may have diabetes, while another has rheumatoid arthritis.2

Modifiable risk factors

Several modifiable risk factors have been studied in association with RA, including reproductive hormonal exposures, tobacco use, dietary factors, and microbial exposures.

Smoking

Among all risk factors, the strongest and most consistent evidence is for an association between smoking and RA. A history of smoking is associated with a modest to moderately (1.3—2.4 times) increased risk of RA onset. This relationship between smoking and RA is strongest among people who are ACPA-positive (anti-citrullinated protein/peptide antibodies), a marker of autoimmune activity.

Reproductive and breastfeeding history

Hormones related to reproduction have been studied extensively as potential risk factors for RA.

Oral contraceptives (OC): Early studies found that women who had ever used OCs had a modest to moderately decreased in risk of RA. The decreased risk has not been confirmed in recent studies. The estrogen concentration of contemporary OCs is typically 80—90% less than the first OCs introduced in the 1960s, which may account for the lack of association in recent studies.

Hormone replacement therapy (HRT): There is mixed evidence of an association between HRT and RA onset.

Live birth history: Most studies have found that women who have never had a live birth have a slight to moderately increased risk of RA.

Breastfeeding: Recent population-based studies have found that RA is less common among women who breastfeed.

Menstrual history: At least two studies have observed that women with irregular menses or a truncated menstrual history (e.g. early menopause) have an increased risk of RA.3